ACP InternistWeekly

In the News for the Week of February 11, 2014

Highlights

Lower-dose statins plus combination therapies may be an alternative for patients intolerant of or unresponsive to high-dose
statins

Clinicians could cautiously consider using a lower-intensity statin combined with a bile acid sequestrant or ezetimibe for
high-risk patients intolerant of or unresponsive to statins, a meta-analysis found. More...

More MIs in men 90 days after starting testosterone therapy, study finds

Receiving a prescription for testosterone therapy was associated with increased risk of myocardial infarction (MI) in the
next 90 days, a recent study found. More...

Test yourself

MKSAP Quiz: evaluation of chronic fatigue syndrome

A 32-year-old woman is evaluated following a diagnosis of chronic fatigue syndrome. She has a several-year history of chronic
disabling fatigue, unrefreshing sleep, muscle and joint pain, and headache. Following a physical exam, what is the most appropriate
management for this patient's symptoms? More...

Diabetes

In patients with type 2 diabetes, intensive control of blood pressure and cholesterol did not protect against cognitive decline,
a recent study found. More...

Smoking cessation

Pharmacy chain announces it will no longer sell tobacco products

CVS Caremark announced last week that it would begin to phase out sales of tobacco products in its stores. More...

COPD

Low-dose opioids may safely reduce breathlessness in severe COPD

Lower doses of opioids do not appear to increase hospital admissions or death in patients with very severe chronic obstructive
pulmonary disease (COPD) and may safely reduce symptoms, according to a new study. More...

Health information management

New rule gives patients access to lab test reports

Under a new rule issued last week by the Department of Health and Human Services, patients will have the right to access their
medical lab reports directly from the lab that performed the testing, without having to go through the physician who ordered
the test. More...

Reminder: 2014 Annual HIMSS Conference to be held Feb. 23-27

The 2014 Annual Healthcare Information Management Systems Society (HIMSS) Conference and Exhibition will be held in Orlando,
Fla., Feb. 23-27, 2014, at the Orange County Convention Center. More...

CMS update

Don't miss upcoming deadlines for PQRS

Deadlines for data submission for the Physician Quality Reporting System (PQRS) are fast approaching. More...

Highlights

Lower-dose statins plus combination therapies may be an alternative for patients intolerant of or unresponsive to high-dose
statins

Clinicians could cautiously consider using a lower-intensity statin combined with a bile acid sequestrant or ezetimibe for
high-risk patients intolerant of or unresponsive to statins, a meta-analysis found.

To compare the clinical benefits, adherence, and harms of lower-intensity statin combination therapy and higher-intensity
statin monotherapy among adults at high risk for atherosclerotic cardiovascular disease, researchers conducted a meta-analysis
of 36 randomized, controlled trials.

Combination therapy with bile acid sequestrants or ezetimibe decreased LDL cholesterol at least as well as higher-intensity
monotherapy and 0% to 14% more than mid-intensity monotherapy. Compared to high-intensity monotherapy, a mid-intensity statin
plus ezetimibe decreased LDL cholesterol 5% to 15% in patients with atherosclerotic cardiovascular disease and 3% to 21% in
patients with diabetes.

There were inconsistent effects on lowering LDL cholesterol with a low-intensity statin combined with niacin compared to mid-intensity
statin monotherapy, and no studies looked at ω-3 fatty acids, the analysis reported. There was not enough evidence
to determine long-term clinical outcomes, adherence or potential harms for all regimens.

The authors noted that high-dose statin regimens have been linked to a statistically significant increased risk for adverse
events and resulting nonadherence to therapy. For example, statin users have a 50% greater adjusted odds of musculoskeletal
pain than nonusers. One study found that 4% of patients do not respond and another 10% have inadequate LDL cholesterol reduction.
Given that statin intolerance and unresponsiveness are relatively common, many clinicians will probably care for such patients
at some point, the authors said. However, the combination strategy should be used with caution given the lack of evidence
on long-term clinical benefits and harms.

"When considering combination therapy with a lower-intensity statin and bile acid sequestrant, patients may benefit from counseling
on separating drug administration to ensure maximal effect of each medication," the study noted.

More MIs in men 90 days after starting testosterone therapy, study finds

Receiving a prescription for testosterone therapy was associated with increased risk of myocardial infarction (MI) in the
next 90 days, a recent study found.

The cohort study included more than 50,000 men who had an initial testosterone therapy (TT) prescription between January 2008
and October 2010. Researchers compared the incidence rate of non-fatal MI among these men in the year prior to the prescription
and the 90 days following the prescription. They did the same comparison in more than 150,000 men prescribed phosphodiesterase
type 5 inhibitors (PDE5I). Results were published by PLOS One on Jan. 29.

Overall, the rate ratio (RR) of MI 90 days after a TT prescription compared to the year before was 1.36 (95% CI, 1.03 to 1.81)
in the men studied, while there was no significant change with PDE5I prescriptions. In men age 65 and over, the rate ratio
was 2.19 (95% CI, 1.27 to 3.77) with TT, with, again, no significant difference in MI rates before and after a PDE5I prescription.
The MI risk associated with TT increased with age, from 0.95 for men under age 55 (95% CI, 0.54 to 1.67) to 3.43 for men 75
or older (95% CI, 1.54 to 7.56). PDE5Is showed no such trend. Men under 65 only had an increased risk for MI with a TT prescription
if they had a history of heart disease, but the risk ratio for these patients was particularly high: 2.90 (95% CI, 1.49 to
5.62).

In older men and younger ones with heart disease, initiation of a TT prescription was associated with a substantial increase
in MI risk, the study authors concluded. This finding is consistent with other recent research and supports an association
between TT and risk of serious cardiovascular events, the authors said. Possible explanations include that exogenous testosterone
has different effects from endogenous testosterone and that the circulating estrogens increased by TT may have an effect.

More trials are urgently needed to assess the benefits and risks of TT, including the impact of different doses, duration
and pre-existing conditions in patients, the study authors said. In the meantime, however, "clinicians might be well advised
to include serious cardiovascular events in their discussions with patients of potential risks, particularly for men with
existing cardiovascular disease."

In response to the publication of this study and other recent research, the FDA announced that it is investigating the risk of stroke, heart attack and death in men taking FDA-approved testosterone products. While
this investigation is ongoing, clinicians should consider whether the benefits of TT are likely to exceed potential risks,
the agency advised.

Test yourself

MKSAP Quiz: evaluation of chronic fatigue syndrome

A 32-year-old woman is evaluated following a diagnosis of chronic fatigue syndrome. She has a several-year history of chronic
disabling fatigue, unrefreshing sleep, muscle and joint pain, and headache.

A comprehensive evaluation has not identified any other medical condition, and a screen for depression is normal. Her only
medications are multiple vitamins and dietary supplements. Physical examination is normal.

Which of the following is the most appropriate management for this patient's symptoms?

Diabetes

In patients with type 2 diabetes, intensive control of blood pressure and cholesterol did not protect against cognitive decline,
a recent study found.

This substudy of the ACCORD trial included 2,977 patients with type 2 diabetes, a hemoglobin A1c (HbA1c) of at least 7.5%,
and no evidence of cognitive impairment or dementia at baseline. About half of the patients (n=1,439) were randomized to a systolic blood pressure goal of either under 120 mm Hg or under 140 mm Hg. The other group (1,538
patients) had LDL cholesterol levels less than 100 mg/dL and were randomized to either a fibrate or placebo. Results were published online Feb. 3 by JAMA Internal Medicine.

Cognition was assessed at baseline, 20 months and 40 months in all patients; a subset of 503 patients also underwent brain
magnetic resonance imaging (MRI) at baseline and 40 months. No differences in cognition were found among any of the trial
groups. Among the patients who had brain MRIs, total brain volume by 40 months declined more in the intensive blood pressure
control group than the standard care group (difference, −4.4 cm3; 95% CI, −7.8 to −1.1; P=0.01).

The study authors concluded that intensive blood pressure and lipid therapy did not measurably affect cognitive decline in
the studied patient population. They noted that the studied patients, with a mean HbA1c of 8.3% and disease duration of 10
years, had relatively longstanding and poorly controlled disease. The findings extend the previous observation of the ACCORD
MIND trial that intensive glucose control did not preserve cognitive function in similar patients.

Intensive glucose control did, however, maintain total brain volume more than standard care in that trial, the opposite of
this study's finding with blood pressure control. These results suggest that total brain volume cannot be used as a surrogate
marker for cognitive outcomes, the researchers said. They also noted that cognitive decline is a slow process and that longer-term
data (currently being gathered in an extension of this study) could reveal more subtle differences between the groups. Overall,
though, the results "make clear the decreasing returns of intensive medication-based therapy for advanced [type 2 diabetes],"
the authors concluded.

According to an invited commentary, the study provides reason for exploring other treatments for preventing the cognitive decline associated with diabetes and
a reminder that "enthusiastic control of [blood pressure] later in life should be pursued with caution and based on existing
evidence, not extrapolated benefits."

Smoking cessation

Pharmacy chain announces it will no longer sell tobacco products

CVS Caremark announced last week that it would begin to phase out sales of tobacco products in its stores.

Writing in the Journal of the American Medical Association, Troyen A. Brennan, MD, FACP, CVS Caremark's chief medical officer, and Steven A. Schroeder, MD, director of the Smoking
Cessation Leadership Center at the University of California, San Francisco, called tobacco-related health harms "one of the
most important public health challenges of the 21st century" and noted that "emphasis on restricting availability and reinforcing
the social unacceptability of smoking casts a harsh light on pharmacies' sale of cigarettes and other tobacco products."

In addition, pharmacies' increasing involvement in wellness programs and retail clinics highlights the paradox of offering
tobacco products for sale, the authors said. "The CVS retail pharmacy, pharmacy benefit management, and retail-clinic companies
are, like others, increasingly developing programs to improve the quality of care and reduce health care costs. Selling tobacco
products is clearly antithetical to both goals," the authors wrote. "Although the sale of tobacco products in CVS pharmacies
produces more than $1.5 billion in revenues annually, the financial gain is outweighed by the paradox inherent in promoting
health while contributing to tobacco-related deaths. As a result, CVS has decided to cease tobacco sales in a phased approach
over the next year."

The full commentary was published Feb. 5 and is available free of charge online.

COPD

Low-dose opioids may safely reduce breathlessness in severe COPD

Lower doses of opioids do not appear to increase hospital admissions or death in patients with very severe chronic obstructive
pulmonary disease (COPD) and may safely reduce symptoms, according to a new study.

Researchers performed a population-based longitudinal consecutive cohort study at medical centers in Sweden that prescribed
long-term oxygen therapy. Included patients were 45 years of age and older, began oxygen therapy for physician-diagnosed COPD,
and were entered into a nationwide database between Oct. 1, 2005, and June 30, 2009. The study's objective was to examine
the safety of benzodiazepines and opioids in patients who had very severe COPD. The main outcome measures were the relationship
between benzodiazepines and opioid therapy and admission and mortality rates, with adjustment for age, sex, arterial blood
gases, body mass index, performance status, previous admissions, comorbid conditions and concurrent medications. The study results were published online Jan. 30 by BMJ.

A total of 2,249 patients, 59% of whom were women, were included in the study. At baseline, 535 patients (24%) were taking
benzodiazepines, 509 (23%) were taking opioids, and 200 (9%) were taking both drugs. Overall, 1,681 patients (76%) were admitted
to the hospital, and 1,129 (50%) died during 1.1 years of follow-up.

No association was found between benzodiazepines and opioids and increased rates of hospital admission (hazard ratios, 0.98
[95% CI, 0.87 to 1.10] and 0.98 [95% CI, 0.86 to 1.10], respectively). A dose-response trend toward increased mortality was
seen for benzodiazepines (hazard ratio, 1.21 [95% CI, 1.05 to 1.39]) and for higher doses of opioids (hazard ratio, 1.21 [95%
CI, 1.02 to 1.44]). However, this association was not seen with lower doses of opioids, defined as less than or equal to 30
mg of oral morphine equivalents per day (hazard ratio, 1.03 [95% CI, 0.84 to 1.26]). Lower concurrent doses of benzodiazepines
and opioids were not associated with increased rates of hospital admission or mortality (hazard ratios, 0.86 [95% CI, 0.53
to 1.42] and 1.25 [95% CI, 0.78 to 1.99], respectively). The same associations were seen in patients who were naive to the
study drugs and in those who were hypercapnic.

The authors noted that they could not rule out residual confounding and that patients may not have taken all drugs as prescribed,
among other limitations. However, they concluded that their study supports the safety of lower doses of opioids to reduce
symptoms of breathlessness in patients with severe respiratory disease and indicates that benzodiazepines should not be used
as first-line therapy for symptom reduction in this population.

"Sustained release morphine should be considered as a first line treatment and should be initiated at a low dose regularly
and titrated upward over days and weeks, balancing beneficial and adverse effects," the authors wrote. "Titration up to 30
mg morphine daily might safely improve breathlessness in over 60% of patients, with a mean decrease of 35% in the intensity
of breathless from the person's own baseline." The authors stressed that higher opioid doses for control of symptoms should
be balanced against a potentially increased risk for adverse effects and that all patients should receive adequate follow-up
for their clinical condition and symptoms.

Health information management

New rule gives patients access to lab test reports

Under a new rule issued last week by the Department of Health and Human Services, patients will have the right to access their
medical lab reports directly from the lab that performed the testing, without having to go through the physician who ordered
the test.

ACP was supportive of the proposed rule in the interest of increasing the transparency of a patient's health care information and allowing them
increased control over their personal health information. The new rule takes effect on Oct. 6. Guidance on how it will work
is available from the College online.

Reminder: 2014 Annual HIMSS Conference to be held Feb. 23-27

The 2014 Annual Healthcare Information Management Systems Society (HIMSS) Conference and Exhibition will be held in Orlando,
Fla., Feb. 23-27, 2014, at the Orange County Convention Center. More than 35,000 health care industry professionals are expected
to attend to discuss health IT issues and explore innovative solutions for their organizations.

ACP has endorsed the Physicians' IT Symposium and Meaningful Use Workshop offered at this year's event. The conference will
offer more than 300 peer-reviewed sessions, including workshops and roundtables, and pre-conference symposia on clinical and
business intelligence, health IT and rural care, ICD-10, interoperability, mobile health, nursing informatics, and more.

Hillary Clinton leads a keynote roster that also includes Mark Bertolini, chairman, CEO and president of Aetna. For more information
about HIMSS14 and to register, go online.

CMS update

Don't miss upcoming deadlines for PQRS

Deadlines for data submission for the Physician Quality Reporting System (PQRS) are fast approaching.

The 2013 reporting year will be the last year to participate in PQRS and receive an incentive payment of 0.5% of the total
allowed charges for Medicare Physician Fee Schedule (MPFS)-covered services during 2015. In addition, failure to participate
in PQRS during 2013 triggers a 1.5% reduction in Medicare reimbursement in 2015.

The specific deadlines for the data submission are dependent on a physician's reporting method.

Physicians submitting data through an EHR or claims-based reporting for the 2013 PQRS requirement must have their data and
claims processed by Feb. 28, 2014.

Physicians submitting data through a qualified registry should check with their registry to determine the registry-specific
deadline for physician data submission. Qualified registries have until March 31, 2014, to send their data to CMS; however,
many registries have earlier deadlines for physician data submission.

March 13, 2014, is the deadline for data submission for physicians using the PQRSwizard.

ACP offers several resources to help in meeting the PQRS reporting requirements. The PQRSwizard is an online tool, similar to tax preparation software, designed to help physicians and other eligible professionals quickly
and easily participate in the PQRS requirements. ACP members can purchase the PQRSwizard at a discounted rate. More information available on the Medicare Physician Fee Schedule is available online, as is information on the PQRSwizard.

An instructional video sponsored by the Council of Medical Specialty Societies (CMSS) provides an overview of PQRS reporting options and a demonstration
of the PQRSwizard registry.

For more information on upcoming important dates related to a variety of regulatory, payment, educational and delivery system
changes and requirements, visit ACP's Physician and Practice Timeline.

MKSAP Answer and Critique

The correct answer is C: Graded exercise program. This item is available to MKSAP 16 subscribers as item 72 in the General
Internal Medicine section. More information is available online.

The most appropriate management for this patient is to begin a graded exercise program. Chronic fatigue syndrome (CFS) is
defined as medically unexplained fatigue that persists for 6 months or more and is accompanied by at least 4 of the following
symptoms: subjective memory impairment, sore throat, tender lymph nodes, muscle or joint pain, headache, unrefreshing sleep,
and postexertional malaise lasting longer than 24 hours. Management of CFS is challenging and is geared toward managing symptoms
and maintaining function, rather than seeking cure. A comprehensive, individually tailored approach is required, typically
based on nonpharmacologic therapy, such as lifestyle modification and sleep hygiene. Specific treatment options that have
been demonstrated to improve symptoms include graded exercise programs and cognitive-behavioral therapy (CBT). CBT in this
setting is targeted in part at breaking the cycle of effort avoidance, decline in physical conditioning, and increase in fatigue
and can work well in combination with graded exercise in this regard. CBT reduces fatigue and improves functional status.

Although Epstein-Barr virus and a host of other infectious agents have been considered in the pathogenesis of CFS, none have
been borne out by careful study; therefore, antiviral therapy, including acyclovir, has no role in the treatment of CFS. A
variety of other medications have been tried, including corticosteroids, mineralocorticoids, growth hormone, and melatonin,
but with no clear evidence of benefit, and are not indicated for this patient.

Current evidence is not sufficiently robust to recommend dietary supplements, herbal preparations (evening primrose oil),
homeopathy, or even pharmacotherapy. Patients with concomitant depression should be treated with antidepressants. Although
no specific class of antidepressant is recommended in this setting, tricyclic antidepressants are often utilized in patients
with CFS and depression owing to their adjunct effectiveness in treating muscle pain.

Test yourself

A 54-year-old woman is evaluated for shortness of breath of 3 months' duration and a 4.5-kg (10-lb) weight loss over the preceding 2 months. She has a 35-pack-year smoking history. Following a physical exam and further testing, what is the most appropriate treatment?

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